Risperdal Linked to Stroke; Zyprexa linked to Diabetes

Risperdal Linked to Stroke; Zyprexa linked to Diabetes

Fri, 11 Apr 2003

Two highly promoted, best selling neuroleptic drugs (also called, antipsychotics) are linked to life-threatening drug-induced conditions. The Boston Globe reports (below) that elderly people who are prescribed Risperdal are at increased risk of stroke. The manufacturer, Johnson and Johnson, sent letters of warning to Canadian physicians and pharmacists last October, citing ì37 reports of stroke or related events like blood clots or hemorrhages, including 16 deaths, among patients who have taken its drug. ì

However, the company has not yet sent out similar warning letters to U.S. healthcare professionals. Johnson & Johnson announced that ”An update to the Risperdal label is indeed being made, and we will be sending out letters to health-care professionals soon.” Why the delay? What about warnings in their advertisements that reach patients directly?

The Wall Street Journal reports (abstract below) that warnings have been issued all over the world–except the U.S.ó about the high risk of diabetes for patients prescribed Eli Lillyís Zyprexa. FDA’s own expert team had gathered information about the possible link between atypical antipsychotics and diabetes. However, the WSJ reports, “Officials with the division say that in recent years, they have gradually moved away from requiring manufacturers to warn about “possible” side effects. The division now aims, instead, to define risks with more certainty, the officials say.”

As we all know, there is almost never certainty about a drug’s causal adverse effect.

But there one can infer a probability when it occurs with regularity. Perhaps the FDA’s reluctance to warn the public about potential danger from best selling drugs, is the agency’s commitment to protect the profit margin of drug companies such as Eli Lilly–even if the drug puts patients lives at risk.

NEW YORK — Johnson & Johnson said yesterday it will soon send letters to thousands of US physicians advising them of possible increased risk of stroke among elderly patients taking its blockbuster antipsychotic drug Risperdal.

A Johnson & Johnson spokeswoman said the company also plans to change the package insert label of the pill, which has annual global sales of $2.1 billion, to note possible stroke risk. ”An update to the Risperdal label is indeed being made, and we will be sending out letters to health-care professionals soon.”

The diversified health-care company last October sent a similar warning letter to Canadian doctors and pharmacists.

It cited 37 reports of stroke or related events like blood clots or hemorrhages, including 16 deaths, among patients who have taken its drug. Moreover, the company cited two clinical trials of elderly dementia patients in which ”a higher proportion of patients taking Risperdal experienced strokes or related events than those who received placebo [sugar pills].”

Johnson & Johnson noted in the Canadian warning letter that the elderly are generally at increased risk of stroke.

Risperdal is Johnson & Johnson’s second-biggest-selling medicine. Although only approved for schizophrenia, it is widely used to control behavioral disorders in elderly patients with dementia and Alzheimer’s disease — such as delusions, aggression, and anxiety.

Risperdal and rival schizophrenia drugs already include information in their labels about strokes seen in patients taking them in either clinical trials or after the drugs reached the market. Risperdal’s label will be changed, however, to include more specific information about strokes in the elderly.

Larry Sasich, a pharmacist and research analyst for consumer watchdog group Public Citizen, said worrisome safety trends have cropped up in various clinical trials that tested Risperdal in Alzheimer’s patients. He said 29 cases of stroke and stroke-related events were seen among 764 patients tested in four specific trials, or in about 4 percent of patients, compared with only 2 percent of those who received placebos.

”And there were four deaths among patients taking Risperdal, compared with only one death in those taking placebos,” Sasich said.

”The Risperdal label clearly states that there is no evidence this drug is safe or effective in treating dementia, and it looks like doctors are hurting people by prescribing it for this condition,” Sasich said.

Sasich said the incidence of stroke among elderly Alzheimer’s patients should spur US regulators to further examine whether younger schizophrenia patients are also unacceptably prone to them. ”Public Citizen is ignoring the clinical reality that it would be impossible for many dementia patients to live at home without these drugs,” said Dr. Norman Sussman, a professor of psychiatry at New York University Medical Center.

Sussman said doctors routinely use Risperdal and similar schizophrenia drugs like Eli Lilly and Co.’s Zyprexa to treat dementia symptoms, even though they are not approved for that use.

Abstract: The young woman was hospitalized for a week and released, still taking Zyprexa, in addition to insulin, which controls blood-sugar levels. Dr. [Thomas Johnson] says that neither he nor doctors at the hospital initially considered any potential connection between Zyprexa and the patient’s blood-sugar problem because the drug’s label lacks any alert on the topic. After he found reports on the Internet about the drug and diabetes, he took the patient off Zyprexa. Her blood sugar returned to normal, he says.

A team of researchers, led by Elizabeth Koller, a former FDA official, and Dr. [P. Murali Doraiswamy] of Duke, catalogued the number of diabetes-related complications reported to the FDA in patients taking Zyprexa and Risperdal, the drug made by Johnson & Johnson unit Janssen Pharmaceutica. The researchers reported the possible Zyprexa side-effect cases last July in the journal Pharmacotherapy: Over an eight-year period, 288 diabetes cases, of which 75 resulted in severe illness and 23 in death. Of the millions who had taken Risperdal over an overlapping nine-year period, Dr. Koller’s group found 132 diabetes cases, 31 of which involved life-threatening complications and five that ended in death. The findings were based on voluntary reports to the FDA, which scientists estimate reflect between 1% and 10% of actual cases.

Robert W. Baker, a senior clinical research scientist at Lilly, says the company has spent millions of dollars on research evaluating the diabetes question. Roughly a quarter of Zyprexa patients gain more than 25 pounds while on the medication, Lilly researchers say, and obesity! is linked with diabetes. But Dr. Baker says the evidence suggests Zyp rexa itself doesn’t cause diabetes-related problems. He says the research suggests that the Zyprexa patients who developed diabetes probably had elevated blood-sugar levels before taking the medication.